CN112028872B - A kind of synthetic method of dibenzoselenophene compound - Google Patents

Abstract

The invention discloses a synthetic method for preparing a dibenzoselenophene compound. The method is characterized in that a C-Se bond is formed through the free radical cyclization of a biaryl boric acid substrate catalyzed by TMSCN and selenium powder, so that a dibenzoselenophene compound is constructed. The new strategy has the advantages of no metal participation, no additive promotion, wide substrate range, good functional group compatibility, simple operation, high yield and the like.

Description

A kind of synthetic method of dibenzoselenophene compound

technical field

The application belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing dibenzoselenophene compounds.

Background technique

Selenenophene derivatives have attracted widespread attention in fields such as organic synthetic chemistry, material science, and organic optoelectronic devices, especially in the field of optoelectronic devices, which have shown good performance and have become a new research hotspot in the field of optoelectronic materials. However, the research on the preparation of selenophene derivatives due to the difficulty in the source of the starting material selenophene and the harsh conditions of the preparation process makes the development of selenophene chemistry relatively slow, which greatly affects the rapid development of selenophene chemistry (the preparation of selenophene derivatives and the Advances in Applied Research, Li Chunli et al., "Journal of Henan University (Natural Science Edition)", Vol. 43, No. 3, pp. 258-264, May 2013).

Dibenzoselenophenes are a common basic framework unit in selenophene derivatives, and they appear widely in material molecules. The methods for preparing dibenzoselenophene compounds in the prior art mainly include (1) using diarylselenide compounds as raw materials, and using noble metals Pd, Ag, etc., and/or transition metals such as Cu, Ti, and Mo as catalysts , build a complex and expensive catalytic reaction system to prepare dibenzoselenophene compounds (see ACS Catalysis, 10(4), 2707-2712, 2020; Chemistry of Materials, 31(17), 6598-6604, 2019; Chemical Science, 7(4), 2587-2591, 2016, etc.); (2) Using aryl diselenide compounds as raw materials, in the presence of Mo, Pd and other metal catalysts and/or halogen elements (I ₂ , Br ₂ ), etc. Under the presence of catalytic reaction conditions, dibenzoselenophene is prepared (see US2010072887A; J.Am.Chem.Soc, 72,5753-5754,1950; CN105017302A; European Journal of OrganicChemisty, 2017(39), 5892-5895; Chemistry-A European Journal, 25(8), 1936-1940, 2019; Chemistry-A European Journal, 24(43), 10971-10974, 2018;) (3) Biphenyl dihalide (Br, I) The compound is a raw material, prepared under the condition of selenium dichloride/butyllithium to obtain diaryl and selenophene (CN104125951A), or prepared under the condition of copper/alkali/selenium powder to obtain diaryl and selenophene (Organic Chemistry Frontiers, 5(9). 21), 5756-5759, 2016) etc. Although the prior art discloses a variety of synthetic routes represented by the above, in these methods, it is extremely difficult and expensive to obtain reaction raw materials, coupled with the use of expensive catalytic reaction systems, harsh reaction conditions and complicated operations. , and there are also disadvantages such as poor universality of reaction substrates, low atom economy and low yield of target products, so that those skilled in the art still need to pay a large amount of effort when preparing the required dibenzoselenophene compounds. cost. Based on this, it is particularly important to develop efficient, environmentally friendly and simple methods for the synthesis of dibenzoselenophenes.

SUMMARY OF THE INVENTION

The purpose of the present invention is to enrich the synthetic routes for preparing dibenzoselenophene compounds in the prior art and provide a brand-new synthetic strategy. In this method, TMSCN-catalyzed free radical cyclization of biarylboronic acid substrates and selenium powder forms C-Se bonds to construct dibenzoselenophenes. This new strategy has the advantages of no metal involvement, no additive promotion, wide substrate range, good functional group compatibility, simple operation, and high yield.

Provided according to the present invention is a method for synthesizing a dibenzoselenophene compound, comprising the following steps:

The biarylboronic acid substrate shown in formula a, TMSCN, selenium powder and organic solvent are sequentially added to the reactor, and the reaction mixture is stirred and reacted at 100-150° C. for 4-48 hours in an air atmosphere, and the reaction is complete. After cooling to room temperature, the reaction mixture was diluted with ether, filtered through a pad of silica gel and the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel flash chromatography to obtain the dibenzoselenophene compound represented by formula d.

The reaction formula is as follows:

表示取代或未取代的C_6-20芳环；并且其中，所述“取代或未取代的”中的“取代基”选自卤素、C_1-6烷基、C_1-6烷氧基、C_1-6卤代烷基。in,

Represents a substituted or unsubstituted C _6-20 aromatic ring; and wherein, the "substituent" in the "substituted or unsubstituted" is selected from halogen, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 haloalkyl.

表示取代或未取代的C_6-20芳环、取代或未取代的C_2-20杂芳环；并且其中，所述“取代或未取代的”中的“取代基”选自卤素、C_1-6烷基、C_1-6烷氧基、 C_1-6烷硫基、C_1-6卤代烷基。

Represents a substituted or unsubstituted C _6-20 aromatic ring, a substituted or unsubstituted C _2-20 heteroaromatic ring; and wherein, the "substituent" in the "substituted or unsubstituted" is selected from halogen, C _{1 -6} alkyl, C _1-6 alkoxy, C _1-6 alkylthio, C _1-6 haloalkyl.

表示取代或未取代的苯；并且其中，所述“取代或未取代的”中的“取代基”选自氟、氯、溴、碘、甲基、乙基、丙基、丁基、叔丁基、甲氧基、乙氧基、三氟甲基。Preferably,

Represents substituted or unsubstituted benzene; and wherein the "substituent" in the "substituted or unsubstituted" is selected from fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, butyl, tert-butyl group, methoxy, ethoxy, trifluoromethyl.

表示取代或未取代的苯、萘、蒽、茚、菲或芘；取代或未取代的吲哚、呋喃、苯并呋喃、苯并噻吩、噻吩或吡啶；并且其中，所述“取代或未取代的”中的“取代基”选自氟、氯、溴、碘、甲基、乙基、丙基、丁基、叔丁基、甲氧基、甲硫基、三氟甲基。

Represents substituted or unsubstituted benzene, naphthalene, anthracene, indene, phenanthrene or pyrene; substituted or unsubstituted indole, furan, benzofuran, benzothiophene, thiophene or pyridine; and wherein the "substituted or unsubstituted" The "substituent"in" is selected from fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, butyl, tert-butyl, methoxy, methylthio, trifluoromethyl.

Most preferably, the compound of formula a has the following structure:

According to the aforementioned synthesis method of the present invention, the molar ratio of the biarylboronic acid substrate of formula a, TMSCN and selenium powder is 1:(0.01～0.1):(1～5); preferably, the biarylboronic acid of formula a The molar ratio of boronic acid substrate, TMSCN, selenium powder is 1:(0.01～0.05):(2～4); Most preferably, the feeding of biarylboronic acid substrate of formula a, TMSCN, selenium powder The molar ratio was 1:0.03:3.

According to the aforementioned synthesis method of the present invention, the reaction temperature is preferably 120-140°C, most preferably 140°C. The reaction time is preferably 12-24 hours, preferably 24 hours.

In the present invention, the organic solvent is DMSO. During the experiment, the inventor found that the reaction could not proceed when using other organic solvents, such as 1,4-dioxane, toluene, o-xylene, chlorobenzene or DMF.

The synthetic method of the present invention has achieved the following beneficial technical effects:

The synthesis method of the present invention forms a C-Se bond through the free radical cyclization of a biarylboronic acid substrate and a selenium powder catalyzed by TMSCN to construct a dibenzoselenophene compound, which has not been reported in the prior art. The new strategy has the advantages of readily available raw materials, no metal participation, no need for additive promotion, wide substrate range, good functional group compatibility, simple operation, and high yield of 98%.

Detailed ways

The present invention will be further described below with reference to specific embodiments.

Embodiment 1-10 Reaction condition optimization example

The optimal reaction conditions were screened using [1,1'-biphenyl]-2-ylboronic acid represented by formula 1a as a template substrate. The reaction formula is as follows:

Example 1

A 25 mL Schlenk tube equipped with a stir bar was charged with [1,1'-biphenyl]-2-ylboronic acid of formula 1a (0.2 mmol), Se (0.6 mmol) and DMSO (2 ml), and the reaction mixture was mixed with In an air atmosphere, the mixture was stirred at 140° C. for 24 h, and no reaction was carried out after sampling by TLC and/or GC-MS.

Example 2

A 25 mL Schlenk tube equipped with a stir bar was charged with [1,1'-biphenyl]-2-ylboronic acid of formula 1a (0.2 mmol), TMSCN (1 mol%, ie 0.002 mmol), Se (3 equiv. , ie 0.6 mmol) and DMSO (2 ml). The reaction mixture was stirred at 140 °C for 24 h under air atmosphere. After cooling, the reaction mixture was diluted with 10 mL of ether, filtered through a pad of silica gel and concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel to give the target product phenoxselenide/phenothiaselenide of formula 1d in 40% yield. White solid; ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.24-8.23 (m, 2H), 8.06-8.04 (m, 2H), 7.62-7.59 (m, 2H), 7.56-7.53 (m, 2H); ¹³ C NMR (125 MHz, CDCl ₃ ) δ 139.6, 138.5, 127.1, 126.3, 125.1, 123.1.

Example 3

TMSCN (3mol%, i.e. 0.006mmol), the remaining reaction conditions and operations are the same as in Example 2, and the yield of the target product phenoxselenide/phenothiaselenide shown in formula 1d is 98%

Example 4

The reaction solvent was replaced with 1,4-dioxane, other reaction conditions and operations were the same as those in Example 3, and sampling was detected by TLC and/or GC-MS without reaction.

Example 5

The replacement reaction solvent was toluene, and other reaction conditions and operations were the same as those in Example 3, and sampling was carried out without reaction after TLC and/or GC-MS detection.

Example 6

The replacement reaction solvent was m-xylene, other reaction conditions and operations were the same as those in Example 3, and sampling was detected by TLC and/or GC-MS without reaction.

Example 7

The replacement reaction solvent was chlorobenzene, and other reaction conditions and operations were the same as in Example 3, and sampling was carried out without reaction after TLC and/or GC-MS detection.

Example 8

The replacement reaction solvent was DMF, and other reaction conditions and operations were the same as those in Example 3, and the sampling was detected by TLC and/or GC-MS, and no reaction was carried out.

Example 9

The replacement reaction temperature is 130 ° C, other reaction conditions and operations are the same as in Example 3, and the target product shown in formula 1d, phenoxoselenide/phenothialenide, has a yield of 71%

Example 10

The replacement reaction temperature is 120 ° C, other reaction conditions and operations are the same as those in Example 3, and the target product shown in formula 1d, phenoxoselenide/phenothialenide, has a yield of 56%

The experimental results of the above reaction conditions showed that the use of 3 mol% of TMSCN was essential and sufficient to completely convert [1,1'-biphenyl]-2-ylboronic acid to the product in 98% yield. The desired product was not obtained in the absence of TMSCN. Appropriately lowering the temperature will reduce the reaction yield. Interestingly, the product could not be obtained using other solvents.

Example 11-29 Reaction Substrate Expansion Example

After determining the optimal reaction conditions, the inventors next explored the adaptability range of arylboronic acid substrates. Using the arylboronic acid compounds shown in the aforementioned formulas 2a-9a as raw materials, under the optimal reaction conditions of Example 3, the universality of the optimal reaction conditions was investigated, and the compounds shown in the formulas 2d-9d were prepared respectively. target product. The results are shown in Table 1 below:

Table 1:

The characterization data of compounds 2d to 9d are as follows:

2d: white solid; ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.96-7.94 (m, 2H), 7.80-7.78 (m, 1H), 7.51-7.49 (m, 1H), 7.40-7.37 (m, 1H) ), 7.33-7.30 (m, 1H), 7.13-7.09 (m, 1H); ¹³ C NMR (125MHz, CDCl ₃ ) δ 161.8 (d, J=246.3Hz), 140.4 (d, J=8.8Hz) , 139.1(d,J＝2.5Hz),137.4,134.7(d,J＝2.5Hz),126.6,126.0,125.1,123.7(d,J＝8.8Hz),122.6,113.2(d,J＝22.5Hz) ,112.6(d,J=23.8Hz);19F NMR(470MHz, CDCl ₃ )δ-144.4(s,1F).HRMS(ESI):calculated for C ₁₂ H ₈ FSe[M+H]+250.9770, found 250.9783 .

3d: white solid; ¹ H NMR (500MHz, CDCl ₃ ) δ 8.04-8.02(m, 1H), 7.96-7.95(m, 1H), 7.83-7.82(m, 1H), 7.64(s, 1H), 7.41-7.38 (m, 1H), 7.33-7.30 (m, 1H), 7.23-7.21 (m, 1H), 2.44 (s, 3H); ¹³ C NMR (125MHz, CDCl ₃ ) δ 139.5, 139.0, 138.4, 137.0 , 135.9, 126.4, 126.3, 126.2, 126.1, 124.8, 122.6, 122.5, 21.5. HRMS(ESI): calculated for C ₁₃ H ₁₀ SeNa[M+Na]+268.9846, found268.9846.

4d: white solid; ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.04-8.02 (m, 1H), 7.98-7.96 (m, 1H), 7.84-7.83 (m, 1H), 7.72 (s, 1H), 7.44-7.41 (m, 1H), 7.36-7.32 (m, 2H), 2.55 (s, 3H); ¹³ C NMR (125MHz, CDCl ₃ ) δ 140.2, 138.9, 138.0, 137.7, 135.7, 126.6, 126.0, 124.9, 124.1, 123.3, 122.8, 122.6, 16.2. GC-MS (EI, 70 eV): calculated for _{C13H10SSe 277.9668} , found278.0.

5d: white solid; ¹ H NMR (500MHz, CDCl ₃ ) δ 8.34(s, 1H), 8.17-8.15(m, 1H), 7.98-7.97(m, 1H), 7.90-7.89(m, 1H), 7.61-7.59 (m, 1H), 7.51-7.48 (m, 1H), 7.45-7.42 (m, 1H); ¹³ CNMR (125MHz, CDCl ₃ ) δ 143.3, 139.8, 138.4, 137.3, 127.7, 124.6 (q, J =270.0Hz), 127.4, 126.5, 126.1, 125.3, 123.2, 123.0 (q, J=3.8 Hz), 119.6 (q, J=3.8 Hz); ¹⁹ F NMR (470 MHz, CDCl3) δ-61.7 (s, 3F ).

6d: white solid; ¹ H NMR (500MHz, CDCl ₃ ) δ 8.16-8.14 (m, 1H), 8.10-8.09 (m, 1H), 7.96-7.91 (m, 3H), 7.85-7.83 (m, 1H) ), 7.58-7.51(m, 2H), 7.49-7.46(m, 1H), 7.40-7.37(m, 1H); ¹³ C NMR (125MHz, CDCl ₃ )δ139.5, 139.4, 139.3, 135.6, 132.4, 131.4, 128.9, 126.9, 126.4, 126.3, 126.2, 126.1, 126.0, 125.0, 123.1, 120.8. HRMS(ESI): calculated for C ₁₆ H ₁₁ Se[M+H]+283.0021, found 283.0007.

7d: white solid; ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.92-8.90 (m, 1H), 8.72-8.70 (m, 1H), 8.65-8.64 (m, 1H), 8.55-8.54 (m, 1H) ), 7.95-7.93(m, 1H), 7.86-7.84(m, 1H), 7.64-7.61(m, 1H), 7.58-7.46(m, 4H), 7.35-7.32(m, 1H); ¹³ C NMR (125MHz, CDCl ₃ )δ141.5,140.6,139.9,131.0,130.7,130.1,130.0,129.2,127.4,127.3,127.1,127.0,126.6,126.3,125.6,125.3,125.1,123.2.HRMS(ESI) : calculated for C ₂₀ H ₁₃ Se[M+H]+333.0177, found 333.0187.

8d: white solid; ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.02-8.01 (m, 1H), 7.92-7.91 (m, 1H), 7.69-7.67 (m, 1H), 7.65-7.63 (m, 1H) ), 7.49-7.46(m, 1H), 7.39-7.35(m, 1H), 7.35-7.33(m, 1H), 7.32-7.30(m, 1H); ¹³ C NMR (125MHz, CDCl ₃ )δ157.9 , 154.4,141.5,127.4,127.3,126.4,125.4,125.2,124.9,123.3,121.4,119.9,115.6, 112.4.HRMS(ESI):calculated for C ₁₂ H ₉ OSe[M+H]+272.9813,found272.9819.

9d: white solid; ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.09-8.07 (m, 2H), 7.99-7.97 (m, 1H), 7.67 (s, 1H), 7.64-7.62 (m, 1H), 7.27-7.26 (m, 1H), 2.47 (s, 3H); ¹³ C NMR (125MHz, CDCl ₃ ) δ 141.2, 140.6, 139.0, 138.4, 134.6, 128.2 (q, J=32.5Hz), 127.5, 126.7, 126.2 , 125.4, 123.2 (q, J=3.8 Hz), 122.5, 121.7 (q, J=3.8 Hz), 21.6; ¹⁹ F NMR (470 MHz, CDCl ₃ ) δ-61.6 (s, 3F). GC-MS (EI , 70eV): calculated for C ₁₄ H ₉ F ₃ Se 313.9822, found 314.0.

The test results of the universality research on the expansion of reaction substrates show that the synthesis strategy of the present invention is suitable for ring A being a benzene ring or a substituted benzene ring, ring B being a benzene ring with electron donating or electron withdrawing groups, and a fused aromatic ring. Or aromatic heterocycles and other reaction substrates with different structures and/or substituents, and all of them can be prepared in moderate to excellent yields to obtain the corresponding target products. This shows that the preparation method of the present invention has good universality for various arylboronic acid substrates under the optimal process conditions.

Claims (8)

1. a synthetic method of dibenzoselenophene compound, comprises the steps: The biaryl boronic acid substrate shown in formula a, TMSCN, selenium powder and organic solvent are sequentially added to the reactor, and the reaction mixture is stirred and reacted at 100-150° C. for 4-48 hours in an air atmosphere, and the reaction is complete. After cooling to room temperature, the reaction mixture was diluted with ether, filtered through a silica gel pad and the filtrate was concentrated under reduced pressure, and then the residue was purified by silica gel flash chromatography to obtain the dibenzoselenophene compound represented by formula d; The reaction formula is as follows:

in,

Represents a substituted or unsubstituted C _6-20 aromatic ring; and wherein, the "substituent" in the "substituted or unsubstituted" is selected from halogen, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 haloalkyl;

Represents a substituted or unsubstituted C _6-20 aromatic ring, a substituted or unsubstituted C _2-20 heteroaromatic ring; and wherein, the "substituent" in the "substituted or unsubstituted" is selected from halogen, C _{1 -6} alkyl, C _1-6 alkoxy, C _1-6 alkylthio, C _1-6 haloalkyl; And wherein, the organic solvent is DMSO. 2. synthetic method according to claim 1, is characterized in that,

Represents substituted or unsubstituted benzene; and wherein the "substituent" in the "substituted or unsubstituted" is selected from fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, butyl, tert-butyl base, methoxy, ethoxy, trifluoromethyl;

Represents substituted or unsubstituted benzene, naphthalene, anthracene, indene, phenanthrene or pyrene; substituted or unsubstituted indole, furan, benzofuran, benzothiophene, thiophene or pyridine; and wherein the "substituted or unsubstituted" The "substituent"in" is selected from fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, butyl, tert-butyl, methoxy, methylthio, trifluoromethyl. 3. synthetic method according to claim 2 is characterized in that, formula a compound has following structure:

4. synthetic method according to claim 1 is characterized in that, the molar ratio of biarylboronic acid substrate of formula a, TMSCN, selenium powder is 1:(0.01～0.1):(1～5). 5. synthetic method according to claim 4 is characterized in that, the molar ratio of biarylboronic acid substrate of formula a, TMSCN, selenium powder is 1:(0.01～0.05):(2～4). 6. synthetic method according to claim 5 is characterized in that, the molar ratio of biarylboronic acid substrate of formula a, TMSCN, selenium powder is 1:0.03:3. 7 . The synthesis method according to claim 1 , wherein the reaction temperature is 120-140° C., and the reaction time is 12-24 h. 8 . 8. synthetic method according to claim 7 is characterized in that, reaction temperature is 140 ℃, and reaction time is 24 hours.